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DOI: 10.17650/2070-9781-2023-24-2-126-129
Изменение показателей эякулята
после инфекции COVID-19: новая, требующая
V ■ V
исследований, эра физической активности
BY 4.0
A.M.A. Ismail
Department of Physical Therapy for Cardiovascular/Respiratory Disorder and Geriatrics, Faculty of Physical Therapy, Cairo University; Cairo, Egypt
Контакты: Ali Mohamed Ali Ismail ali-mohamed@cu.edu.eg
Для цитирования: Ismail A.M. A. Изменение показателей эякулята после инфекции COVID-19: новая, требующая исследований, эра физической активности. Андрология и генитальная хирургия 2023;24(2):126-9. (На англ.). DOI: 10.17650/2070-9781-2023-24-2-126-129
Letter to editor
Post-COVID changes of semen parameters: a new era for physical activity that needs investigation
A.M.A. Ismail
Department of Physical Therapy for Cardiovascular/Respiratory Disorder and Geriatrics, Faculty of Physical Therapy, Cairo University; Cairo, Egypt
Contacts: Ali Mohamed Ali Ismail ali-mohamed@cu.edu.eg
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For citation: Ismail A.M. A. Post-COVID changes of semen parameters: a new era for physical activity that needs investigation. Andrologiya i genital'naya khirurgiya = Andrology and Genital Surgery 2023;24(2):126-9. (In Engl.). DOI: 10.17650/ 2070-9781-2023-24-2-126-129
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Dear editor,
Coronavirus disease 2019 (COVID-19) predominantly affects the respiratory system, but it can also have an impact on the male reproductive systems [1, 2].
SAR-CoV-2 functions through a variety of methods that could impair male reproduction [3]. Via inflammatory reactions, it activates oxidant-sensitive pathways and causes oxidative stress. According to reports, the overproduction of reactive oxygen species (ROS) during SARS-CoVinfections may primarily activate the NF-kB (nuclear factor kappa-light-chain-enhancer of activated B-cells) and toll-like receptor (mostly TLR-4) pathways. This increases the release of cytokines, which intensifies the inflammatory responses [4]. Moreover, it has been observed that this virus may result in orchitis, which can lower the quality of the semen and induce
OS, spermatogenic disturbances, and germ cell death [5]. Moreover, SARS-CoV-2 infection causes psychological stress, which is a key pathway to systemic OS [3]. In addition to the direct link between SARS-CoV-2 infection and OS, antiviral medications like ribavirin, used to treat COVID-19, are also thought to cause OS, lower testosterone levels, hinder spermatogenesis, lower sperm counts, and create malformed sperm. Furthermore, it has been claimed that ribavirin use is linked to DNA fragmentation of sperms for up to eight months after the end of treatment [6].
Reduced semen quality and endocrine abnormalities as well as lipid peroxidation of sperm membranes and intracellular oxidative damage to spermatozoa, most notably sperm DNA breakage, have been documented as macro- and microlevel effects of OS on testicular functioning [3, 7]. Given that
the inherent integrity of the sperm DNA controls the success rate of fertilization and subsequent embryo development, these OS-induced damages in particular may have a negative impact on reproductive outcomes [8].
Angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease (TMPRSS2) receptors are used by the SARS-CoV-2 virus to enter human cells. The spermatogonia, Sertoli, and Leydig cells in the testes as well as the prostate epithelial cells are thought to express both the ACE2 and TM-PRSS2 receptors in the male reproductive system. It is documented that 18 % of infected patients report scrotal discomfort may be due to ACE2 expression in the testicular tissues. ACE2 expression is correlated with severe impairment in spermatogenesis. Now, it is fair to assume that the virus may be detected in semen by altering the blood-testis barrier or by excretion into prostatic fluid if receptors for the virus are present at various percentages in the male reproductive system [9].
The Coronavirus interacts with human spermatozoa and impairs fertility in patients with positive SARS-CoV-2 results. The COVID-19 infection's suppression of semen volume, progressive motility, morphology, sperm count, and DNA integrity was associated with increased seminal markers of oxidative stress and inflammation [10].
In males who recovered from COVID-19, despite the absence of a positive finding of SARS-CoV-2 in the post-COVID seminal sample/analysis, except for sperm morphology, all semen parameters (concentration, volume [2], sperm motility, and total motile sperm count) were impaired [2, 11]. Anti-oxi-dative pharmacological agents may be the available treatment to increase sperm count motility and morphology and to restore the negative impact of COVID-19 on men's sperm vitality [10].
Lifestyle changes (increasingphysical activity) have been suggested as adjunctive treatment modalities to address some post-COVID complications that manifest in the male genital systems, such as erectile dysfunction [12—15] which is defined as inability to maintain or attain penile erection sufficient for sexual intercourse [16, 17], but up until this point, no medical trends have been focused on utilizing the advantages of exercise to improve post-COVID related changes in semen parameters.
People that are physically active appear to produce more high-quality semen and have a more anabolic hormonal environment than sedentary subjects. In physically active people, an improvement in morphology and total progressive motility of sperms has been noted. This is demonstrated/explained by the measured hormonal values, which are higher in physically active men than in sedentary ones. Testosterone, follicle-stimulating hormone (promotes initiation and progression of spermatogenesis), and luteinizing hormone (promotes testosterone secretion) are examples of these hormones that are associated with high-quality semen in physically active men [18].
Furthermore, previous research has shown that, in contrast to what happens with more intense training (i. e. high intensity exercise) and some forms of training (i. e. cycling), moder-ate-intensityphysical activity either positively influences basal values of such hormones or at the very least does not have
negative effects on them [19]. Male fertility may be adversely impacted by using high-intensity cycling, as it was demonstrated that the levels of seminal cytokines (interleukin-1, inter-leukin-6, and interleukin-8) increased and/or remained high after 30-days recovery from high-intensity cycling and that semen parameters (volume, sperm motility, sperm morphology, sperm concentration, and the number of spermatozoa) decreased during this 30-day period [20].
On the other hand, long-term moderate-intensity exercise can enhance pregnancy rates in wives of men with low seminal quality, improve seminal proinflammatory cytokines and redox homeostasis, attenuate seminal peroxidative biomarkers and DNA fragmentation index, improve standard semen quality parameters, and increase activity and concentration of seminal enzymatic anti-oxidants [21].
Exercising at a moderate pace may replace or support the suggested treatment, antioxidant therapies, in men with low semen quality due to the anti-oxidative properties of moderate-intensity exercise. Moderate-intensity exercise may result in a more proper environment for the sperm production processes due to the modest/moderate production of free radicals used in the anti-oxidative activities within testicles, in contrast to the high production rate of free radicals during high-intensity exercise that induces oxidative damage and tissue injury [22].
COVID is associated with low semen quality due to the low production of antioxidative enzymes [13, 14]. The induction of antioxidant enzymes via moderate-intensity exercise seems to be related to the activation of spermatogenesis-relatedfactors such as nuclear factor kappa B and mitogen-activated protein kinase [23]. These factors not only improve spermato-genesis but also enhance sperm functions (motility and fertilization potential), hence the selection of moderate-intensity exercise programs may be more suitable than high-intensity ones to improve semen quality in men with low semen quality [18].
COVID is associated with high inflammatory markers and cytokines within different body parts/systems including testes [13, 14]. The anti-inflammatory effect of lifelong or long-term ^ moderate exercise training in the testis is confirmed by decreased levels of pro-inflammatory mediators/markers, (inter-leukin-1 and tumor necrosis factor-alpha) and elevated levels £ of testis anti-inflammatory markers (interleukin-10 and trans- ° forming growth factor alpha). Testicularfunctions are promoted by inhibiting or lowering oxidative stress and inflammation ^ as a response to long-term exercise training. Indeed, in experimental studies, testosterone levels in the serum and testes are higher in rats that were exercised continuously. Higher levels of S two steroidogenic enzymes, steroidogenic acute regulatory protein x and Cyp11a, which are in charge of the initial stages of stero- ^ idogenesis, are found in exercised rats more than in sedentary x rats. In addition, an increased number of Leydig cells and sper- * matogonia in seminiferous tubules are reported. The above-men- ¡3 tioned observations suggest increased testosterone and semen m production/quality in exercised men [24].
Exercise-induced weight loss may improve post-COVID metabolic dysfunctions such as insulin resistance, elevated
leptin and lipids, increased systemic inflammatory markers, and central obesity [25] (the source of increased aromatase production which increases testosterone conversion to estrogen). Improvement in these metabolic dysfunction increases testosterone production which may increase semen quality/production [26] in post-COVID men with low semen quality.
Additionally, complementary therapies [27] including physical activity levels and exercise regimens are well-known moderators of the clinical symptoms and prognosis in many chronic diseases [28], including post-COVID-related issues including fatigue, chest pain, sleeplessness, coughing, weakened immunity, dyspnea, etc. The psychological conditions (stress, sadness, and anxiety) that are thought to contribute to reduced semen quality in men may be improved by treating these post-COVID symptoms.
Additionally, exercise may strengthen the immune system, which is typically impaired in post-COVID men with reproductive/genital system issues. The following are some of the hypothesized mechanisms by which exercise may boost immunity in different body parts including the reproductive/genital system: (a) increasing T-lymphocytes, neutrophils, macrophages, and monocytes, which are essential components of the body's defense system against infectious diseases; (b) increasing immunoglobulin levels; and (c) preventing the rise of high circulating levels of C-reactive protein andpro-inflam-matory markers [13, 14]. Correction of systemic inflammatory milieu may be associated with improvement in the localized testicular inflammation, hence sperm production and quality may improve.
A cardiopulmonary exercise test is a very needed prerequisite before incorporating post-COVID men in a structured physical program to detect the maximum affordable level of exercise by every patient. The physical status of the recovering men may be impaired by the severity level of COVID-19 affection and/or drugs consumed during the course of the disease and/or recovery phases. Selecting men who recovered from mild or moderate attacks of COVID are good candidates [13, 14] for searching the effect of exercise on low semen quality because they can safely tolerate the performance of cardiopulmonary exercise tests or exercise sessions.
Also, selecting walking programs is safe than other activities such as cycling. Cycling may raise testicular tissue heat and mechanical trauma which induces inflammatory cascades within testicular tissues that negatively impact anti-oxidants and the health of seminal parameters of subjects involved in long-term cycling programs [20], hence avoiding cycling activities in exercise programs directed to post-COVID men with low semen quality is preferred but this suggestion needs a future investigation.
Designing supervised physical activity programs with or without antioxidant agents may be suggested to decrease the negative impact of COVID on semen quality and parameters, especially in those with concomitant cardiovascular comor-bidities (diabetes and obesity) but the intensity of exercise (moderate or high) and form of exercise (walking, swimming, resistance exercise, etc.) need confirmed investigations in future exercise studies dealing with post-COVID men with low semen quality.
ЛИТЕРАТУРА/REFERENCES
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1. K09 E., Keseroglu B.B. Does COVID-19 worsen the semen parameters? Early results of a Tertiary Healthcare Center. Urol Int 2021;105(9-10):743-8. DOI: 10.1159/000517276
2. Yildirim O., Gultekin M.H., Aygun G. et al. Changes of sperm parameters in men recovered from COVID-19: a comparision between pre-COVID and post-COVID period. Eur Urol 2022;81:S1206. DOI: 10.1016/S0302-2838(22)00893-4
3. Dutta S., Sengupta P. SARS-CoV-2 and male infertility: possible multifaceted pathology. Reprod Sci 2020;28(1):23-6.
DOI: 10.1007/s43032-020-00261-z
4. Li R., Yin T., Fang F. et al. Potential risks of SARS-Cov-2 infection on reproductive health. Reprod Biomed Online 2020;41(1):89-95. DOI: 10.1016/j.rbmo.2020.04.018
5. Xu J., Qi L., Chi X. et al. Orchitis: a complication of severe acute respiratory syndrome (SARS). Biol Reprod 2006;74(2):410-6. DOI: 10.1095/biolreprod.105.044776
6. Pecou S., Moinard N., Walschaerts M. et al. Ribavirin and pegylated interferon treatment for hepatitis C was associated not only with semen alterations but also with sperm deoxyribonucleic acid fragmentation in humans. Fertil Steril 2009;91(3):933.e17-e22. DOI: 10.1016/j.fertnstert.2008.07.1755
7. Dutta S., Majzoub A., Agarwal A. Oxidative stress and sperm function: a systematic review on evaluation and management. Arab J Urol 2019;17(2):87-97. DOI: 10.1080/2090598X.2019.1599624
8. Selvam M.K.P., Sengupta P., Agarwal A. Sperm DNA fragmentation and male infertility. In: Genetics of Male Infertility.
Ed. by M. Arafa, H. Elbardisi, A. Majzoub, A. Agarwal. Springer, Cham, 2020. P. 155-172. DOI: 10.1007/978-3-030-37972-8_9 9. Pan F., Xiao X., Guo J. et al. No evidence of severe acute
respiratory syndrome-coronavirus 2 in semen of males recovering from coronavirus disease 2019. Fertil Steril 2020;113(6):1135-9. DOI: 10.1016/j.fertnstert.2020.04.024
10. Sen Sharma D. Covid 19 and male infertility-how long should fertility treatment be deferred to overcome the postcovid changes in semen parameters and to restore male fertility? Hum Reprod 2022;37(Suppl 1):deac104.019. DOI: 10.1093/humrep/deac104.019
11. Pazir Y., Eroglu T., Kose A. et al. Impaired semen parameters
in patients with confirmed SARS-CoV-2 infection: a prospective cohort study. Andrologia 2021;53(9):e14157. DOI: 10.1111/and. 14157
12. Parohan M., Yaghoubi S., Seraji A. et al. Risk factors for mortality in patients with Coronavirus disease 2019 (COVID-19) infection:
a systematic review and meta-analysis of observational studies. Aging Male 2020;23(5):1416-24. DOI: 10.1080/13685538.2020.1774748
13. Ismail A.M.A. Erectile dysfunction: the non-utilized role
of exercise rehabilitation for the most embarrassing forgotten post-COVID complication in men. Aging Male 2022;25(1):217-8. DOI: 10.1080/13685538.2022.2108013
14. Ismail A.M.A. Post-COVID erectile dysfunction: the exercise may be a good considered complementary choice. Am J Mens Health 2022;16(4):15579883221114983. DOI: 10.1177/ 15579883221114983
15. Adeyemi D.H., Odetayo A.F., Hamed M.A., Akhigbe R.E. Impact of COVID 19 on erectile function. Aging Male 2022;25(1):202-16. DOI: 10.1080/13685538.2022.2104833
16. Ismail A.M.A., Abdelghany A.I. Effect of adding a 2-month consequent continuous and interval elliptical aerobic training to once-daily 5-mg tadalafil administration on erectile dysfunction in obese men. Sex Disabil 2022;40(1):129-39. DOI: 10.1007/s11195-021-09720-0
17. Ismail A.M.A., Shaaban Abd El-Azeim A. Response of erectile dysfunction to extracorporeal shock wave therapy in type 2 diabetic men. Physiother Quart 2022;30(4):77-80. DOI: 10.5114/ pq.2022.121151
18. Vaamonde D., Da Silva-Grigoletto M.E., García-Manso J.M. et al. Physically active men show better semen parameters and hormone values than sedentary men. Eur J Appl Physiol 2012;112(9):3267— 73. DOI: 10.1007/s00421-011-2304-6
19. White L.J., Dressendorfer R.H., Ferguson M.A., Wade C.E. Maintenance of testosterone status in fitness joggers after increased training mileage. Eur J Appl Physiol 2002;86(6):498-502.
DOI: 10.1007/s00421-001-0575-z
20. Hajizadeh Maleki B., Tartibian B. Long-term Low-to-Intensive Cycling Training: Impact on Semen Parameters and Seminal Cytokines. Clin J Sport Med 2015;25(6):535-40. DOI: 10.1097/ JSM.0000000000000122
21. Hajizadeh Maleki B., Tartibian B. Moderate aerobic exercise training for improving reproductive function in infertile patients:
a randomized controlled trial. Cytokine 2017;92:55-67. DOI: 10.1016/j.cyto.2017.01.007
22. Sachdev S., Davies K.J. Production, detection, and adaptive responses to free radicals in exercise. Free Radic Biol Med 2008;44(2):215-23. DOI: 10.1016/j.freeradbiomed.2007.07.019
23. Kostaropoulos I.A., Nikolaidis M.G., Jamurtas A.Z. et al. Comparison of the blood redox status between long-distance and short-distance runners. Physiol Res 2006;55(6):611-6.
DOI: 10.33549/physiolres.930898
24. Matos B., Howl J., Ferreira R., Fardilha M. Exploring the effect of exercise training on testicular function. Eur J Appl Physiol 2019;119(1):1-8. DOI: 10.1007/s00421-018-3989-6
25. Ismail A.M.A. Is there an effect of lifestyle changes on psoriasis-associated erectile dysfunction? Am J Mens Health 2022;16(5): 15579883221128117. DOI: 10.1177/15579883221128117
26. Ismail A.M.A., Abdelghany A.I., Atef H. Response of testosterone and semen parameters to a 14-week aerobic training in sedentary obese men with hyperglycaemia. Physiother Quart 2023;31(1): 28-33. DOI: 10.5114/pq.2023.123525
27. Ismail A.M.A. Complementary role of Benson's relaxation technique in post orgasmic illness syndrome. Aging Male 2023;26(1):2174511. DOI: 10.1080/13685538.2023.2174511
28. Ismail A.M.A. Is there a role for exercise in men suffering from HIV-induced erectile dysfunction. Aging Male 2023;26(1):2174512. DOI: 10.1080/13685538.2023.2174512
ORCID автора / ORCID of author
A.M.A. Ismail: https://orcid.org/0000-0003-1447-8817
Конфликт интересов. Автор заявляет об отсутствии конфликта интересов. Conflict of interest. No potential conflict of interest was reported by the author.
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Статья поступила: 15.02.2023. Принята к публикации: 22.03.2023. Article received: 15.02.2023. Accepted for publication: 22.03.2023.
